Inhalation toxicity study of formamide in rats

Formamide is a widely used solvent for the manufacture and processing of plastics, and the possibility for inhalation exposure exists for workers. To assess the toxicity of repeated inhalation of sublethal concentrations of formamide, three groups of 10 male Crl:CD BR rats each were exposed nose-only for 6 hr/day, 5 days/week for 2 weeks to design concentrations of 100, 500, or 1500 ppm of formamide vapor in air. A control group of 10 male rats was exposed simultaneously to air only. At the end of the exposure period, blood and urine samples were collected for clinical analyses, and 5 rats per group were killed for pathologic examination. The remaining 5 rats per group were retained for a 14-day postexposure observation (recovery) period and then subjected to the same clinical and pathologic examinations. Male rats exposed to 1500 ppm had significantly depressed body weights and body weight gains during the exposure and recovery periods compared to controls. Clinical pathologic examinations revealed that decreased platelet and/or lymphocyte counts were observed in rats exposed to 500 or 1500 ppm of formamide. Pathologic examinations revealed compound-related microscopic changes in the kidneys of rats exposed to 1500 ppm formamide. Minimal to severe necrosis and regeneration of renal tubular epithelial cells were observed principally in the outer stripe of the outer medulla and in cortical medullary rays. Based upon the hematologic and clinical chemical parameters measured, the no-observed-effect exposure concentration for repeated inhalation of formamide was considered to be 100 ppm, under the conditions of this study. The findings of treatment-related microscopic lesions in the kidneys as well as increases in mean absolute kidney weights and kidney-to-body weight ratios reflect the target organ toxicity.